Molecular Mechanisms Underlying Animal Circadian Rhythm

Research in our laboratory focuses on the regulation of circadian clock and its control over organismal physiology. Circadian clocks regulate molecular oscillations that manifest into physiological and behavioral rhythms. The self-sustained molecular oscillator can be synchronized to daily and seasonal environmental changes, thus allowing organisms to perform necessary tasks at biologically advantageous times of day. Analyses of mammalian and Drosophila transcriptomes using DNA microarrays identified a large number of clock-controlled genes that are involved in diverse physiological processes. Besides being indispensable for the control of daily activities in animals, such as the sleep-wake cycle, locomotor activity, hormone circulation and food intake, defects in circadian rhythms and clock genes have also been implicated in a wide range of human disorders, including chronic sleep orders, various forms of depression, metabolic syndromes, as well as susceptibility to cancer and drug and alcohol addiction.

Although circadian clock genes are not highly conserved across kingdoms (plant, animal, fungi, and bacteria), the regulation of circadian oscillators in all organisms studied to date appears to be variations on the same theme. In general, circadian pacemakers are comprised of a set of species and tissue-specific clock genes that are cell-autonomous and autoregulatory through a series of interconnected transcriptional-translational feedback loops. The circadian oscillator is capable of receiving input signals from external time cues, thereby synchronizing its activity to the environment; and can control cell and organismal physiology by regulating the rhythmic expression of downstream effectors in cell and tissue-specific manners. One feature of the oscillator that is inherent in its design is the rhythmic expression of a number of clock RNAs and daily oscillations in clock protein abundance. Despite the centrality of cycling clock mRNA expression, more recent studies have highlighted the importance of post-translational mechanisms, in particular phosphorylation, in regulating clock protein abundance. In addition, posttranslational modifications of clock proteins are believed to regulate their transcriptional activity, subcellular localization, and protein-protein interaction.

Using a combination of biochemical, molecular genetics, and proteomic approaches, we hope to understand the biochemical and cellular basis of clocks, and the mechanisms by which they regulate organismal physiology.

Genetics and Genomics of Insecticide Resistance

The new invasive pest, Spotted Wing Drosophila (Drosophila suzukii), has the potential to become an economic pest of berry crops in California. Data on Spotted Wing Drosophila biology is urgently needed to develop effective management strategies to protect growers from damage and substantial economic loss. In recent years, molecular and circadian rhythm biology of the closely related Drosophila melanogaster has provided information and techniques that could be useful to managing these long-established vinegar flies. D. melanogaster and other vinegar flies are occasional pests of processing berries, however Spotted Wing Drosophila prefers fresh fruit and would be expected to have different biology and a more detrimental impact on berry production. To complement ongoing studies on Spotted Wing Drosophila phenology and monitoring strategies funded through a regional USDA-SCRI grant to our collaborator Professor Frank Zalom (UC Davis Entomology), we are studying the chronobiology (circadian and seasonal rhythm) of the Spotted Wing Drosophila, specifically examining their daily activity rhythms, time-of-day differences in pesticide efficacy, correlations between pesticide effectiveness and circadian patterns of detoxification gene expression, and how all these factors vary with changing temperatures across seasons. By integrating circadian rhythm biology and pest management, we hope to develop more effective and economical, yet sustainable approaches to combat the Spotted Wing Drosophila.

Our research is currently funded by:

National Science Foundation

National Institute of Health

United States Department of Agriculture

Clarence & Estelle Albaugh Endowment

The California Cherry Board

Washington Tree Fruit Research Commission

California Department of Food and Agriculture